Cantwell began as an Alaskan Railroad flag stop. The village was named for the Cantwell River, the original name of the Nenana River. It is a common gas-up and stretch-your-legs stop for motorists driving the Parks Highway between Anchorage and Fairbanks or the Denali Highway between Cantwell and Paxson.

Cantwell visitor services include lodging, RV Parks and camping, guiding & flying services such as the Atkins Guiding and Flying Service. Cantwell businesses are clustered around the intersection of the Denali and Parks highways and located west on the access road to downtown Cantwell. Options include the Backwoods Lodge, Cantwell Food Mart Parkway Gift Shop, Cantwell RV Park, Parks Highway Service and Towing and multiple gas stations.